Quickly soluble oral film dosage containing steviosides as a unpleasant taste masking agent

ABSTRACT

Disclosed is a quickly soluble oral film dosage for masking a nasty taste, in particular, a quickly soluble oral film dosage comprising a stevioside based sweetener and a high potency sweetener in a ratio by weight (w/w) of 1:3 to 3:1, which may efficiently mask a bitter or nasty taste of a medicine and may be quickly dissolved in a mouth without water, thereby improving an aftertaste thereof thus enhancing dosage acceptability of a patient.

BACKGROUND OF THE INVENTION

This application claims priority to Korean Patent Application No.10-2009-0057276, filed on Jun. 25, 2009 and Korean Patent No.10-2010-0057450, filed on Jun. 17, 2010, in the Korean IntellectualProperty Office, the entire contents of which are hereby incorporated byreference.

FIELD OF THE INVENTION

The present invention relates to a quickly soluble oral film dosage foreffectively masking a unpleasant taste and, more particularly, to aquickly soluble oral film dosage comprising a stevioside based sweetenerand a high potency sweetener in a ratio by weight (w/w) of 1:3 to 3:1,which may efficiently mask a bitter or nasty taste of a medicine and maybe quickly dissolved in a mouth without water, thereby improving anaftertaste thereof thus enhancing dosage acceptability of a patient.

BACKGROUND OF THE RELATED ART

A social distribution ratio of aged population has currently increasedowing to an extended span of human life. Old people generally showdegenerated abilities including eyesight, hearing, memory, physicalstrength, etc. as well as pharmacokinetic variation, thus requiringsuitable medical therapy. Especially, since they have difficulties inswallowing typical tablets or capsules, an alternative oral dosageformulation for aged persons may be required.

A quickly soluble film easily disintegrated or dissolved in a mouth canbe taken without water, thus being useful for aged persons who havedifficulties in swallowing tablets or capsules, handicapped children,patients in bed, and the modern people living a busy life, and so forth.For aged persons and children, a liquid type formulation may beprescribed instead of tablets and/or capsules. However, such liquidformulation has disadvantages such as deteriorated stability andincorrect dosage.

In particular, when a drug is absorbed in an oral mucosa, it may avoidpassage of the drug through the liver. Therefore, the quickly solublefilm dosage is preferably used for some medicines subjected to livermetabolism.

However, a film formulation easily dissolved in an oral cavity enables adrug to be absorbed in the oral mucosa, causing a bitter or nasty tasteof the drug during absorption. Accordingly, ideas for blocking ormasking such bad taste may be required.

In view of the foregoing circumstances, International Patent PublicationNo. WO 2001/70194 describes preparation of a quickly soluble oral filmdosage as a taste masking agent by adsorbing active ingredients to anion-exchange resin. However, the ion-exchange resin contained in awater-soluble polymer may cause scratches during forming and require acomplicated processing.

International Patent Publication No. WO 2003/070227 describes use of achemical compound such as sodium hydrocarbonate generating carbondioxide so as to mask taste. However, sodium hydrocarbonate haslimitations in masking a strong bitter taste.

International Patent Publication No. WO 2008/040534 describes a filmformulation disintegrated and entered into the stomach without adhesionto the oral mucosa. However, the foregoing film formulation is preparedby a complicated method for considerably preventing absorption of theformulation to the oral mucosa and may not provide beneficial effectsfor protection of the stomach and bowels.

U.S. Patent Laid-Open No. US 2008/0044454 describes a preparation methodof a uniform film comprising coating of an active material by a varietyof coating techniques then introducing the coated active material into afilm forming agent. Such coating process may complicate the preparationof film.

SUMMARY OF THE INVENTION

The present inventors have made efforts to overcome the foregoingshortcomings and found that use of at least one selected from a groupconsisting of aspartame, acesulfame potassium, sucralose and neotametogether with stevioside and/or its derivative can mask a bitter and/ornasty taste even without substantially altering a process of preparingan oral film dosage.

In other words, in order to solve conventional problems and to developan improved quickly soluble oral film dosage containing activeingredients as the most preferable formulation, a great deal of studiesand investigation have been conducted by the present inventors. As aresult, they found that the bitter and/or nasty taste may be efficientlymasked without additional coating processes if stevioside and/orderivatives thereof having a strong sweet aftertaste among high potencysweeteners are used together with any typical high potency sweetener,and then, completed the present invention.

Accordingly, it is an object of the present invention to provide aquickly soluble oral film dosage including a therapeutically effectiveamount of active pharmaceutical ingredient, stevioside and/or itsderivative, at least one high potency sweetener, a film forming agent,and at least one of pharmaceutically available additives.

Another object of the present invention is to provide a quickly solubleoral film dosage capable of efficiently masking a nasty taste caused bya therapeutically effective amount of active pharmaceutical ingredientand, in addition, being promptly dissolved in an oral cavity.

In order to achieve the above objects, the present invention provides aquickly soluble oral film dosage, comprising: at least one water-solublepolymer; at least one active pharmaceutical ingredient; a steviosidebased sweetener as an aftertaste enhancer; and at least one high potencysweetener (a primary sweetening agent) as a taste masking agent.

The proposed oral film dosage has excellent effects of masking a nastytaste and may be easily prepared by a simple process at low cost,thereby being preferably used in various applications such as an oralcleanser, a bad breath remover, a carrier for a nutrient supplementaryagent, and a tongue soluble formulation enabling absorption of drugs inthe oral cavity as well as the stomach and bowels, and so forth.

BRIEF DESCRIPTION OF THE DRAWINGS

These and other objects, features, aspects, and advantages of thepresent invention will be more fully described in the following detaileddescription of examples, taken in conjunction with the accompanyingdrawings. In the drawings:

FIG. 1 is a graph showing results of dissolution experiments for aquickly soluble oral film dosage prepared at pH 1.2 according to Example9 of the present invention in comparison with a control (Zofran® Zydistablet available from GlaxoSmithKline Co., 8 mg);

FIG. 2 is a graph showing blood concentration profiles forpharmacokinetic tests using Ondansetron film dosage (8 mg) and Zofran®Zydis tablet (8 mg);

FIG. 3 is a graph showing blood concentration profiles forpharmacokinetic tests in comparison of Sildenafil Citrate film dosage(25 mg) and Viagra® tablet (25 mg);

FIG. 4 is a graph showing blood concentration profiles for oraladministration tests to Beagle dogs using montelukast sodium film dosage(5 mg) and Singulair® chewable tablet (5 mg); and

FIG. 5 is a graph showing sweetness profiles of high potency sweeteners(primary sweetening agents) according to an exemplary embodiment of thepresent invention; as shown in FIG. 5, acesulfame potassium (ACK),aspartame (AST) and stevioside (STS) exhibit delayed expression ofsweetness in sequential order.

DETAILED DESCRIPTION OF THE INVENTION

The present invention describes a composition for a quickly soluble oralfilm dosage comprising active pharmaceutical ingredients, capable ofefficiently masking a nasty taste as well as being rapidly dissolved inan oral cavity.

A preferred film dosage according to the present invention may include aactive pharmaceutical ingredients, stevioside and/or its derivative, atleast one high potency sweetener (a primary sweetening agent), a filmforming agent, and at least one additional component described below.

Examples of the additional component may include pharmaceuticallyavailable additives such as a salivation stimulator, a thickener, afiller, a plasticizer, a secondary sweetening agent, an acidic agent, aflavor, an emulsifier, a surfactant, a binder, a preservative, apigment, a coolant, and the like. Components of such additives will bedescribed in great detail.

In the present invention, a quickly soluble film is obtained bydissolving a drug with a nasty taste, a high potency sweetener (aprimary sweetening agent), stevioside and/or its derivative forimproving an aftertaste in water or oil, emulsifying the solution,adding a water-soluble polymer and other additives to the emulsifiedsolution, and forming the mixture into a shaped film.

As described above, the quickly soluble film of the present inventioncontains the primary sweetening agent with high potency sweetness, thatis, the high potency sweetener.

According to an exemplary embodiment, the high potency sweetener (theprimary sweetening agent) may include at least one sweetener selectedfrom a group consisting of aspartame, acesulfame salts, sucralose,saccharine salts, neotame, cyclamate salts, thaumatin, Luo han guoextract and licorice extract. The high potency sweetener more preferablyincludes at least one selected from a group consisting of aspartame,sucralose, neotame and acesulfame salts.

In case of chemicals with a strong nasty taste, they have a strongbitter taste and nasty taste in an aftertaste thereof. Adding 0.1 to 10wt. % of stevioside based sweetener, that is, stevioside and/or itsderivative relative to the total weight of the chemicals may mask thebitter and/or nasty taste.

Examples of stevioside may include Steviten Light (containing at least98% of stevioside), Steviten Rich (containing 100% of enzyme treatedstevia), Stevia extract REB-A 73% (containing at least 73% ofRebaudioside A), and Rebaten 97(containing at least 97% of RebaudiosideA) etc., all of which are manufactured by DaePyung Co. Ltd. in Korea.

Among these, the enzyme treated stevia is a product with improved tasteprepared using sugar transferase in order to add glucose to the steviaextract, thus reducing an inherent bitter taste of stevioside whileincreasing solubility thereof. The stevia extract Rebaten 97% shows thehighest sweetness and the most excellent equality of sweetness amongseven (7) kinds of sweet ingredients contained in stevia and is obtainedfrom stevia by an alternative separation process.

As for maximum sweetness of each of high potency sweeteners after thelapse of time shown in FIG. 5, acesulfame potassium (ACK) firstlyexpresses the maximum sweetness, followed by aspartame, sucralose andstevioside in sequential order. Therefore, a nasty taste remained aftera drug is absorbed in an oral cavity may be controlled by steviosidemost slowly expressing sweetness.

The quickly soluble oral film dosage of the present invention mayinclude a water-soluble polymer.

Examples of the water-soluble polymer may include pullulan, gelatin,pectin, low viscosity pectin, hydroxypropylmethyl cellulose, lowviscosity hydroxylpropylmethyl cellulose, hydroxyethyl cellulose,hydroxypropyl cellulose, carboxymethyl cellulose, polyvinylalcohol,polyacrylic acid, methyl methacrylate copolymer, carboxyvinyl polymer,polyethyleneglycol, alginic acid, low viscosity alginic acid, sodiumalginate, modified starch, casein, whey protein extract, soy proteinextract, zein, levan, elsinan, gluten, acacia gum, carageenan, Arabicgum, guar gum, locust bean gum, xanthan gum, gellan gum, agar, and thelike.

Preferably, the water-soluble polymer may include at least one selectedfrom a group consisting of pullulan, gelatin, pectin, low viscositypectin, low viscosity alginic acid, hydroxypropylmethyl cellulose, andmodified starch.

An amount of such water-soluble polymer in the quickly soluble film mayrange from 50 to 90 wt. %, preferably 60 to 80 wt. %, and morepreferably 60 to 70 wt. % relative to the total weight of the quicklysoluble film.

The active pharmaceutical ingredient used in the quickly soluble filmmay be any of pharmacologically active substances for oraladministration, in particular, be capable of being quickly dissolved torapidly express efficacy of a medicine. Examples of such substances mayinclude: diabetic remedy such as glimepiride, pioglitazone, etc.;insomnia remedy such as zolpidem, eszopiclone, etc.; genitor-urinaryremedy such as tolterodine, trospium, etc.; obesity remedy such assibutramine; enzyme formulation such as streptokinase; gastric ulcerremedy such as omeprazole; cough remedy and expectorant such astheophylline, clenbuterol, etc.; dermal disorder remedy such asfinasteride; antiemetic drug such as ondansetron; anti-depression drugsuch as fluoxetine; antihistamine drug such as fexofenadinehydrochloride; antipyretic, analgesic and antiphlogistic remedy such asaspirin, ibuprofen, ketoprofen, meloxicam, etc.; hormone drug such astestosterone; circulatory organ remedy such as felodipine, atorvastatin,amlodipine camsylate, doxazosin, simvastatin, lercanidipine, etc.;gastrointestinal remedy such as famotidine, ranitidine, lansoprazole,etc.; heart vascular disease remedy such as amlodipine, nitroglycerin,etc.; psychoneurotic drug such as paroxetine; impotency remedy such assildenafil, tadalafil, vardenafil, etc.; Alzheimer's disease remedy suchas donepezil; osteoporosis remedy; arthritis remedy; epilepsy remedy;muscle relaxing agent; cerebral function enhancer; schizophrenia remedy;immuno-suppression agent; antibiotic agent such as ampicillin,amoxicillin; anticancer agent; Supportives in tumor therapy; vaccine;oral cleanser; anemia remedy; constipation remedy; allergy remedy;anti-blood coagulation agent; oral vaccine; melatonin; vitamin;nutrient; probiotic preparation, multi-symptom cold/flue medications;health functional foods, and so forth.

The active pharmaceutical ingredient may be at least one selected from agroup consisting of triclosan, cetylpyridium chloride, domiphen bromide,quaternary ammonium salt, zinc compounds, sanguinarine, fluoride,alexidine, octenidine, EDTA, aspirin, acetaminophen, ibuprofen,ketoprofen, diflunisal, fenoprofen calcium, naproxen, tolmetin sodium,indomethacin, benzonatate, caramiphen, edisylate, menthol,dextromethorphan hydrobromide, chlophedianol hydrochloride,diphenhydramine, pseudoephedrine hydrochloride, phenylephrine,phenylpropanolamine, pseudoephedrine sulfate, bromophenylamine maleate,chlorophenylamine maleate, carbinoxamine maleate, clemastine fumarate,dexchlorpheniramine maleate, diphenhydramine hydrochloride,diphenhydramine citrate, diphenylpyraline hydrochloride, doxylaminesuccinate, promethazine hydrochloride, pyrilamine maleate,tripelennamine citrate, triprolidine hydrochloride, acrivastine,loratadine, brompheniramine, dexbrompheniramine, guaifenesin, ipecac,calcium iodide, terpine hydrate, loperamide, famotidine, ranitidine,omeprazole, lansoprazole, aliphatic alcohol, nicotine, caffeine,strychnine, picrotoxin, pentylenetetrazol, phenylhydantoin,phenobarbital, primidone, carbamazepine, ethosuximide, methosuximide,phensuximide, trimethadione, diazepam, benzodiazepine, phenacemide,pheneturide, acetazolamide, sulthiame, bromide, levodopa, amantadine,morphine, heroin, hydromorphone, methophone, oxymorphone, levorphanol,codeine, hydrocodone, xycodone, nalorphine, naloxone, naltrexone,salicylate, phenylbutazone, indomethacin, phenacetin, chloropromazine,methotrimeprazine, haloperidol, clozapine, reserpine, imipramine,tranylcypromine, phenelzine, lithium, apomorphine, sildenafil,tadalafil, vardenafil, ondansetron, donepezil, zolpidem tartrate,granisetron, montelukast, pholcodine, butylscopolamine, fentanylcitrate, oxycodone hydrochloride, buprenorphine hydrochloride,escitalopram oxalate, rivastigmine tartrate, esomeprazole magnesium,aripiprazole, zolmitriptan, rizatriptan benzoate, telmisartan,risperidone, benzocaine, cetirizine hydrochloride, bambuterolhydrochloride, galantamine hydrobromide, lercanidipine hydrochloride,paroxetine hydrochloride, meloxicam, tolterodine tartrate, doxazocinmesylate, and pharmaceutically available salts thereof.

If one of the ondansetron salts is an ondansetron hydrochloride, aquickly soluble film including the ondansetron hydrochloride as theactive pharmaceutical ingredient may have bioequivalence.

If one of the montelukast salts is a montelukast sodium, a quicklysoluble film including the montelukast sodium as the activepharmaceutical ingredient may have bioequivalence.

If one of the sildenafil salts is a sildenafil citrate, a quicklysoluble film including the sildenafil citrate as the activepharmaceutical ingredient may have bioequivalence.

An amount of such active ingredient may range from 0.1 to 30 wt. %,preferably 10 to 20 wt. % relative to the total weight of the quicklysoluble film.

The filler may reduce greasy features of the film in the mouth and endowa skeleton structure to the film. In addition, adhesion between films isdecreased while a film disintegration speed and a drug elution rate aswell as stickiness may be controlled. An amount of the filler may rangefrom 1 to 15 wt. % relative to the total weight of the quickly solublefilm.

As for an exemplary embodiment, the filler may include at least oneselected from a group consisting of microcrystalline cellulose,cellulose polymer, magnesium carbonate, calcium carbonate, limestonepowder, silicate, clay, talc, titanium dioxide and calcium phosphate.

A plasticizer may be used to regulate flexibility of the film. An amountof the plasticizer in the quickly soluble film may range from 0.1 to 15wt. % relative to the total weight of the quickly soluble film.

As for an exemplary embodiment, the plasticizer may be at least oneselected from a group consisting of sorbitol, maltitol, xylitol,glycerin, polyethyleneglycol, propyleneglycol, hydrogenated starchsyrup, starch syrup, triacetin, glycerol oleate, sucrose fatty acidester and double chain fatty acid.

The quickly soluble film of the present invention may further include asecondary sweetening agent in an amount of 0.1 to 10 wt. % relative tothe total weight of the quickly soluble film.

As for an exemplary embodiment, the secondary sweetening agent may be atleast one selected from a group consisting of sucrose, glucose, maltose,oligosaccharides dextrin, alpha cyclodextrin, beta cyclodextrin, gammacyclodextrin, methyle beta cyclodextrin, hydroxypropy beta cyclodextrin,cluster dextrin, indigestible dextrin, hydrogenated indigestibledextrin, invert sugar, fructose, lactose, galactose, starch syrup,sorbitol, maltitol, xylitol, erythritol, hydrogenated starch syrup,mannitol and trehalose.

The quickly soluble film of the present invention may further include anacidic agent. The acidic agent serves to control taste together with thesweetener and may function to stimulate secretion of saliva in order todissolve the quickly soluble film. An amount of the acidic agent mayrange from 0.1 to 10 wt. % relative to the total weight of the quicklysoluble film.

As for an exemplary embodiment, the acidic agent may be at least oneselected from a group consisting of citric acid, malic acid, fumaricacid, tartaric acid, ascorbic acid, succinic acid, adipic acid andlactic acid.

The quickly soluble oral film dosage of the present invention mayfurther include flavor. The inventive film dissolved and absorbed in anoral cavity may need appropriate flavor. Such flavor may natural flavor,artificial flavor or a mixture thereof.

The natural flavor may include aromatic plants, especially, extractand/or oil obtained from leaves, flowers, fruits of the aromatic plants.The plant oil may include spearmint oil, cinnamon oil, peppermint oil,lemon oil, clove oil, bay oil, thyme oil, cedar leaf oil, nutmeg oil,sage oil, almond oil, and the like. The artificial flavor may includesynthetic fruit flavors such as lemon, orange, grape, lime, strawberry,etc. and other synthetic flavors such as vanilla, chocolate, coffee,cocoa, pine leaf, ginseng, red ginseng, citrus, etc.

An amount of such flavor depends on various parameters such as types,kinds and/or desired levels of the flavors commonly used in the art and,may range from 1 to 15 wt. % relative to the total weight of the quicklysoluble film.

When the oiltype flavor is used, an emulsifier may be added in order toenable the flavor to be miscible with water-soluble substances. Anamount of the emulsifier depends on kind or amount of the flavor and mayrange from 0.1 to 10 wt. % relative to the total weight of the quicklysoluble film.

As for an exemplary embodiment, the emulsifier may be at least oneselected from a group consisting of glycerin fatty acid ester, sucrosefatty acid ester, lecithin, enzyme treated lecithin, polysorbate,sorbitan fatty acid ester and propyleneglycol.

The quickly soluble oral film dosage of the present invention mayfurther include an appropriate pigment. An amount of the pigment isvaried as needed and may range from 0.01 to 10 wt. % relative to thetotal weight of the quickly soluble film. The pigment may includenatural and/or synthetic pigment.

The quickly soluble oral film dosage may further include a coolingagent. The cooling agent is not particularly limited but includes, forexample, WS3, WS23 or questice-L. An amount of the cooling agent isvaried as needed and may range from 0.01 to 5 wt. % relative to thetotal weight of the quickly soluble film.

The present invention provides a quickly soluble film comprising aquickly soluble oral film dosage composition.

The inventive film is preferably a thin film to maintain desired tensilestrength and other physical strength even in the form of very thin film.As for an exemplary embodiment, the quickly soluble film may have athickness of 20 μm to 200 μm and, preferably, 40 μm to 100 μm.

The present invention provides a method for preparation of a quicklysoluble oral film dosage.

As an exemplary embodiment of the present invention, the method forpreparation of a quickly soluble film includes:

(1) preparing a quickly soluble film composition comprising an activeingredient, at least two high potency sweeteners and a water-solublepolymer;

(2) introducing the prepared film composition into a molding machine toform a film at 50 to 80□; and (3) ageing the formed film for 1 to 10days under 50 to 70% relative humidity.

The method for preparation of the quickly soluble oral film dosageaccording to the present invention may be performed by the followingprocesses.

(1) Solution Preparing Process

a) Preparation of first solution: The water-soluble polymer is placed inboiling water to be completely dissolved.

b) Preparation of second solution: Additives such as a pigment, asweetener, an acidic agent and/or a filler are combined together toprepare the second solution.

c) Preparation of third solution: All of an active ingredient, menthol,a flavor and a cooling agent are mixed with an emulsifier to prepare thethird solution.

d) Preparation of fourth solution: Blending the second and thirdsolutions results in the fourth solution.

e) Preparation of fifth solution: After raising the temperature to 60□or more, the fourth solution is combined with the first solution toprepare the fifth solution.

(2) Forming Process

After filtering the fifth solution, the filtered solution is introducedinto a molding machine to form a film. The temperature of the moldingmachine ranges from 50 to 80□ and produces the film in a roll form via abelt drum drier.

(3) Ageing Process

The formed film is subjected to an ageing process for 1 to 10 days under50 to 70% relative humidity, so as to have a water content suitable forslitting or cutting. Such water content may range from 8 to 12%.

In addition, the following processes may be further performed after theabove processes.

(4) Cutting Process

After slitting the aged roll of film into smaller rolls, the smallerrolls are cut into desired sizes followed by putting them in containersand/or aluminum foils.

(5) Packaging Process

The containers and/or aluminum foils having the products are packagedinto small boxes or manufactured into final products through blistering.

According to the foregoing preparation method, the present invention mayprovide the quickly soluble film without a nasty taste only by addingstevioside and/or its derivative, regardless of applying specifictechniques to coat active ingredients contained in the film.

Also, the quickly soluble film prepared according to the presentinvention may be rapidly disintegrated and dissolved by saliva in amouth without requiring water, so as to be easily administrated to apatient, aged person and/or child who have difficulties in swallowingtypical tablets.

Hereinafter, the present invention will be described in greater detailby the following examples. However, these examples are intended forillustrative purposes and a person skilled in the art will appreciatethat the present invention is not restricted thereto.

EXAMPLES Examples 1 to 3 and Comparative Examples 1 to 3

Meloxicam as an active pharmaceutical ingredient was added to preparefilms having constitutional compositions shown in the following Table 1.Six (6) adult men and women orally took the prepared films. A timeperiod spent for completely dissolving the film with saliva in an oralcavity was measured and a sensory test was performed. The sensory testwas randomly conducted and test results are show in the following Table2.

TABLE 1 Com- Com- Com- parative parative parative exam- exam- exam-Exam- Exam- Exam- ple 1 ple 2 ple 3 ple 1 ple 2 ple 3 Ingredient (wt. %)(wt. %) (wt. %) (wt. %) (wt. %) (wt. %) Aspartame 2.5 2.5 Sucralose 2.52.5 Acesulfame 2.5 2.5 potassium Steviten- 3.5 rich Enzyme 3.5 treatedstevia Rebaten 97% 3.5 Citric acid 0.6 0.6 0.6 0.6 0.6 0.6 Oxidated 5 55 5 5 5 starch Lecithin 0.4 0.4 0.4 0.4 0.4 0.4 Menthol 0.5 0.5 0.5 0.50.5 0.5 Carageenan 0.2 0.2 0.2 0.2 0.2 0.2 Polysorbate 0.4 0.4 0.4 0.40.4 0.4 80 Peppermint 0.8 0.8 0.8 0.8 0.8 0.8 oil Pullulan 66.6 66.666.6 63.1 63.1 63.1 Micro- 3 3 3 3 3 3 crystalline cellulose Lemonflavor 2 2 2 2 2 2 Meloxicam 18 18 18 18 18 18 Total weight 100.0 100.0100.0 100.0 100.0 100.0 * an input amount of each component wascalculated under the presumption that a water content of the preparedfilm is 10%.

As a result of the foregoing sensory test, it was found that thecompositions not containing stevioside and/or its derivative(Comparative Example 1, 2 and 3) and the compositions containing thesame (Examples 1, 2 and 3) showed no substantial difference in terms ofdisintegration time in the mouth. However, the compositions containingstevioside had superior effects of masking a nasty taste over thecompositions without stevioside. These results are shown in Table 2.

As for raw materials used, herein, aspartame and oxidated starch weremanufactured by Daesang Co. Ltd., acesulfame potassium was manufacturedby Nutrinova GmbH, sucralose was manufactured by Tate and Lyle plc,carageenan was manufactured by MSC, polysorbate was manufactured byIlsin Wells, pullulan was manufactured by Hayashibara Co. Ltd., andpeppermint oil and lemon flavor were manufactured by Bolak Co. Ltd.

TABLE 2 Sensory test result Disinte- Initial sensory test gration timeresult of result in mouth sensory after 1 Sweetener (sec) test minuteCompar- Aspartame 55 1 5 ative example 1 Compar- Sucralose 53 1 4 ativeexample 2 Compar- Acesulfame 54 1 5 ative potassium example 3 Exam-Aspartame + 51 1 1 ple 1 steviten-rich Exam- Sucralose + 52 1 1 ple 2enzyme treated stevioside Exam- Acesulfame 53 1 1 ple 3 potassium +rebaten 97% * As the test result value increases, a nasty taste isstrong.

Examples 4 to 8 and Comparative Examples 4 to 8

After altering kinds of the water-soluble polymers and using meloxicamas a active pharmaceutical ingredient films having constitutionalcompositions shown in the following Tables 3 and 4 were prepared. Six(6) adult men and women orally took the prepared films. A time periodspent for completely dissolving the film with saliva in an oral cavitywas measured and a sensory test was performed. The sensory test wasrandomly conducted and test results are show in the following Table 5.

TABLE 3 Exam- Exam- Exam- Exam- Exam- ple 4 ple 5 ple 6 ple 7 ple 8Ingredient (wt. %) (wt. %) (wt. %) (wt. %) (wt. %) Sucralose 2.5 2.5 2.52.5 2.5 Steviten-rich 3.5 3.5 3.5 3.5 3.5 Citric acid 0.6 0.6 0.6 0.60.6 Hydroxypropyl 5 5 5 5 5 starch Lecithin 0.4 0.4 0.4 0.4 0.4 Menthol0.5 0.5 0.5 0.5 0.5 Carageenan 0.2 0.2 0.2 0.2 0.2 Polysorbate 80 0.40.4 0.4 0.4 0.4 Peppermint oil 0.8 0.8 0.8 0.8 0.8 Low viscosity 63.1pectin Gelatin 63.1 HPMC 63.1 Low viscosity 63.1 alginic acid Polyvinyl63.1 alcohol Microcrystalline 3 3 3 3 3 cellulose Lemon flavor 2 2 2 2 2Meloxicam 18 18 18 18 18 Total weight 100.0 100.0 100.0 100.0 100.0 * Aninput amount of each component was calculated under the presumption thata water content of the prepared film is 10%.

TABLE 4 Comparative Comparative Comparative Comparative ComparativeExample Example Example Example Example Ingredient 4 (wt. %) 5 (wt. %) 6(wt. %) 7 (wt. %) 8 (wt. %) Sucralose 2.5 2.5 2.5 2.5 2.5 Citric acid0.6 0.6 0.6 0.6 0.6 Hydroxypropyl 5 5 5 5 5 starch Lecithin 0.4 0.4 0.40.4 0.4 Menthol 0.5 0.5 0.5 0.5 0.5 Carageenan 0.2 0.2 0.2 0.2 0.2Polysorbate 80 0.4 0.4 0.4 0.4 0.4 Peppermint oil 0.8 0.8 0.8 0.8 0.8Low viscosity 66.6 pectin Gelatin 66.6 HPMC 66.6 Low viscosity 66.6alginic acid Polyvinyl 66.6 alcohol Microcrystalline 3 3 3 3 3 celluloseLemon flavor 2 2 2 2 2 Meloxicam 18 18 18 18 18 Total weight 100.0 100.0100.0 100.0 100.0 * An input amount of each component was calculatedunder the presumption that a water content of the prepared film is 10%,

As a result of the foregoing sensory test, it was found that thedisintegration time in the mouth was substantially the same and thenasty taste masking effects were excellent, regardless of differentkinds of water-soluble polymers. These results are shown in Table 5.

As raw materials used, herein, the low viscosity pectin was GENU pectinDSS manufactured by CP Kelco ApS, gelatin was 100 Bloom productsmanufactured by Geltech, hydroxypropylmethyl cellulose was Demacol HE5/6 By manufactured by Demasa, the low viscosity alginic acid was Loginmanufactured by MSC, and hydroxypropyl starch was products manufacturedby Grain Processing Corp.

TABLE 5 Disinte- Initial Sensory test Water gration time result ofresult soluble in mouth sensory after 1 Sweetener polymer (sec) testminute Exam- Sucralose + Pectin 57 1 1 ple 4 steviten- rich Compar-Sucralose Pectin 59 1 4 ative example 4 Exam- Sucralose + Gelatin 54 1 1ple 5 steviten- rich Compar- Sucralose Gelatin 55 1 4 ative example 5Exam- Sucralose + HPMC 53 1 1 ple 6 steviten- rich Compar- SucraloseHPMC 54 1 4 ative example 6 Exam- sucralose + Alginic 56 1 1 ple 7steviten- acid rich Compar- Sucralose Alginic 58 1 4 ative acid example7 Exam- Sucralose + PVA 53 1 1 ple 8 steviten- rich Compar- SucralosePVA 54 1 4 ative example 8 * As the test result value increases, a nastytaste is strong.

Examples 9 to 13 and Comparative Examples 9 to 13

As active pharmaceutical ingredients, ondansetron zolpidem tartrate,tadalafit, lercanidipine, and/or donepezil were added to prepare filmshaving constitutional compositions shown in the following Table 6. Table7 shows constitutional compositions without stevioside.

According to the constitutional compositions shown in Tables 6 and 7,the films were prepared. Six (6) adult men and women orally took theprepared films. A time period spent for completely dissolving the filmwith saliva in an oral cavity was measured and a sensory test wasperformed.

The sensory test was randomly conducted and test results are show in thefollowing Table 8.

TABLE 6 Exam- Exam- Exam- Exam- Exam- ple 9 ple 10 ple 11 ple 12 ple 13Ingredient (wt. %) (wt. %) (wt. %) (wt. %) (wt. %) Sucralose 1 1.2Aspartame 4 3 3 1 1.2 Acesulfame 1 potassium Rebaten 97% 4 3 2 1 1.2Citric acid 0.2 0.2 0.2 0.6 0.6 Hydroxypropyl 4 4 2 0.3 4 starchLecithin 0.1 0.5 0.1 0.4 0.4 Menthol 0.4 2.3 0.3 3 3 Carageenan 0.1 0.10.1 0.1 0.2 Polysorbate 80 0.4 0.5 0.3 0.3 0.3 Peppermint oil 0.8 2.70.6 3 3 Pullulan 72.5 59.4 68.2 72.1 68.4 Microcrystalline 1.4 1.4 0.70.7 4 cellulose Lemon flavor 2 2 1.5 1.5 1.5 Ondansetron 10.1 Zolpidemtartrate 20.9 Tadalafil 20.0 Lercanidipine 15 Donepezil 10 Total weight100.0 100.0 100.0 100.0 100.0 * An input amount of each component wascalculated under the presumption that a water content of the preparedfilm is 10%.

TABLE 7 Comparative Comparative Comparative Comparative ComparativeExample Example Example Example Example Ingredient 9 (wt. %) 10 (wt. %)11 (wt. %) 12 (wt. %) 13 (wt. %) Sucralose 1 1.2 Aspartame 4 3 3 1 1.2Acesulfame 1 potassium Rebaten 97% 0 0 0 0 0 Citric acid 0.2 0.2 0.2 0.60.6 Hydroxypropyl 4 4 2 0.3 4 starch Lecithin 0.1 0.5 0.1 0.4 0.4Menthol 0.4 2.3 0.3 3 3 Carageenan 0.1 0.1 0.1 0.1 0.2 Polysorbate 800.4 0.5 0.3 0.3 0.3 Peppermint oil 0.8 2.7 0.6 3 3 Pullulan 76.5 62.470.2 73.1 70.6 Microcrystalline 1.4 1.4 0.7 0.7 4 cellulose Lemon flavor2 2 1.5 1.5 1.5 Ondansetron 10.1 Zolpidem 20.9 tartrate Tadalafil 20.0Lercanidipine 15 Donepezil 10 Total weight 100.0 100.0 100.0 100.0100.0 * An input amount of each component was calculated under thepresumption that a water content of the prepared film is 10%.

As a result of the foregoing sensory test, it was found that thedisintegration time in the mouth was substantially the same regardlessof different kinds of active ingredients while addition of steviosideexhibited excellent effects of masking an aftertaste which remainedafter 1 minute. These results are shown in Table 8.

TABLE 8 Disinte- Initial Sensory test gration time result of result inmouth sensory after 1 Sweetener (sec) test minute Exam- aspartame + 53 11 ple 9 Rebaten 97% Compar- Aspartame 54 1 5 ative example 9 Exam-Aspartame + 49 1 ple 10 Rebaten 97% Compar- Aspartame 50 1 5 ativeexample 10 Exam- Aspartame + 51 1 1 ple 11 acesulfame potassium +Rebaten 97% Compar- Aspartame + 52 1 4 ative acesulfame example 11potassium Exam- Sucralose + 53 1 1 ple 12 aspartame + Rebaten 97%Compar- Sucralose + 55 1 4 ative aspartame example 12 Exam- Sucralose +52 1 1 ple 13 aspartame + Rebaten 97% Compar- Sucralose + 53 1 4 ativeaspartame example 13 * As the test result value increases, a nasty tasteis strong.

Example 14

Ondansetron based quickly soluble film prepared according to Example 9of the present invention was subjected to dissolution experiments at pH1.2 in comparison with a conventional product named Zofran Zydis tabletcontaining ondansetron available from GlaxoSmithKline Co. (CSK) based onNotice of the Food and Drug Administration and the experimental resultsare shown in FIG. 1. As shown in the accompanying drawings, there was nosubstantial difference in elution between both of the formulations.

Example 15

Ondansetron based quickly soluble film prepared according to Example 9of the present invention was subjected to pharmacokinetic tests incomparison with a conventional product named Zofran® Zydis tabletcontaining ondansetron available from GlaxoSmithKline Co. (GSK). Theexperiments is conducted for healthy fourteen (14) adult men and womenwith Latin square method based on Notice of bioequivalence test standardof the Food and Drug Administration.

The experimental results are shown in Table 9 and FIG. 2. It wasconfirmed that the inventive film of this example has the bioequivalenceas shown in Table 9 and FIG. 2.

TABLE 9 Pharmacokinetic test result of ondansetron film formulationsParameter Group 1 Group 2 AUCO~24(ng · hr/mL) 244.78 ± 91.83  259.64 ±87.10 Cmax(ng/mL) 30.93 ± 10.71 33.16 ± 8.89 Tmax(hr) 1.86 ± 0.71  1.94± 0.75 Note 1) Group 1 is Ondansetron film formulations (8 mg). Group 2is Zorfran ®Zydis ODTs

Example 16 to 20

As active pharmaceutical ingredients, sildenafil free base, sildenafillactate, sildenafil citrate, granisetron, and montelukast sodium wereadded to prepare films having constitutional compositions shown in thefollowing Table 10. The sensory test was randomly conducted and testresults were that unpleasant aftertaste was well masked.

TABLE 10 Exam- Exam- Exam- Exam- Exam- ple 15 ple 16 ple 17 ple 18 ple19 Ingredient (wt. %) (wt. %) (wt. %) (wt. %) (wt. %) Sucralose 1.7 2 21.5 0.5 Neotame 1 2 0 Acesulfame 0.5 0.5 1 0.5 potassium Rebaten 97% 2 22 2 0.5 Citric acid 0.2 0.2 0.2 0.6 0.6 Hydroxypropyl 2 2 2 3 2 starchSpan20 0.1 0.5 0.1 0.4 0.4 Menthol 0.4 2.3 0.3 3 3 Carageenan 0.1 0.10.1 0.1 0.2 Pigment 0.1 0.1 0.1 0.1 0.1 Polysorbate 80 0.4 0.5 0.3 0.30.3 Peppermint oil 0.8 2.7 0.6 3 3 Pullulan 62.3 77.5 55.1 81.5 78.9Microcrystalline 1.4 1.4 0.7 1.5 4 cellulose Beta 0.7 cyclodextrin Lemonflavor 2 2 0.8 1.5 1.5 Sildenafil 25 free base Sildenafil 4.2 lactateSildenafil 35 citrate Granisetron 1 hydrochloride Montelukast 5 sodiumTotal weight 100.0 100.0 100.0 100.0 100.0

Example 21

Sildenafil citrate based quickly soluble film prepared according toExample 18 of the present invention was subjected to pharmacokinetictests in comparison with a conventional product named Viagra® tabletcontaining sildenafil citrate available from Pfizer Inc. The experimentsis conducted for healthy eight (8) adult men and women with Latin squaremethod based on Notice of bioequivalence test standard of the Food andDrug Administration.

The experimental results are shown in Table 11 and FIG. 3. It wasconfirmed that the inventive film of this example has the bioequivalenceas shown in Table 11 and FIG. 3.

TABLE 11 Pharmacokinetic test result of sildenafil citrate filmformulations Parameter Group 1 Group 2 AUCO~24(ng · hr/mL) 711.87 ±89.38 728.64 ± 87.10 Cmax(ng/mL) 255.39 ± 31.17 269.24 ± 88.90 Tmax(hr) 0.83 ± 0.42  0.81 ± 0.35 Note 1) Group 1 is Bexcore sildenafil filmformulations (25 mg). Group 2 is Viagra ® tablets (25 mg)

Example 22

Using the Montelukast based quickly soluble film prepared in mixed ratioaccording to Example 20, as well as a commercially available soliddosage form, that is, Singulair® purchased by Merck & Co., as a controlformulation, respectively, oral administration to Beagle dog wasconducted to compare bioavailability of the foregoing materials.

More particularly, each test specimen was given to six (6) healthy maleBeagle dogs, weighing 10.20 to 12.20 kg (10.99±0.87 kg), and theseanimals were subjected to basal breeding in separate cages for two (2)weeks before experiments. The control formulation administered to Beagledogs was Singulair chewable tablet (5 mg, Merck & Co.), while theinventive test formulation used therein was the formulation prepared inExample 20, which is a quickly soluble film containing 5 mg ofMontelukast relative to 100 mg of the formulation. Beagle dogs weredivided into two groups, each consisting of six (6) animals, and bothgroups received oral administration of the foregoing control formulationand test formulation, respectively. According to any conventional methodfor oral drug administration, 5 mg of the formulation was orallyadministered with water by force-feeding to each Beagle dog.

The experimental results are shown in Table 12 and FIG. 4. It wasconfirmed that the inventive film of this example has the bioequivalenceas shown in Table 12 and FIG. 4.

TABLE 12 Pharmacokinetic test result of montelukast film formulationsParameter Group 1 Group 2 AUCO~24(ng · hr/mL)  12398 ± 3029.7 12151.2 ±1353.3 Cmax(ng/mL) 1010.7 ± 226.7  962.0 ± 73.2 Tmax(hr) 5.3 ± 3.3  4.0± 0.0 Note 1) Group 1 is Bexcore montelukast based quickly soluble filmformulations (5 mg). Group 2 is Singulair ® chewable tablets (5 mg)

Example 23 to 27

As active pharmaceutical ingredients, Galantamine HBr, Doxazosinmesylate, Tolterodine tartrate, paroxetine hydrochloride and bambuterolhydrochloride were added to prepare films having constitutionalcompositions shown in the following Table 13. The sensory test wasrandomly conducted and test results were that unpleasant aftertaste waswell masked.

TABLE 13 Exam- Exam- Exam- Exam- Exam- ple 23 ple 24 ple 25 ple 26 ple27 Ingredient (wt. %) (wt. %) (wt. %) (wt. %) (wt. %) Sucralose 1.6 1.72 1.5 Aspartame 2.5 Acesulfame 0.6 0.5 0.7 0.5 potassium Rebaten 97% 21.9 2 2 1.5 Citric acid 0.2 0.2 0.2 0.6 0.6 Hydroxypropyl 2 2 2 3 2starch Span20 0.1 0.5 0.1 0.4 0.4 Menthol 0.4 2.3 0.3 3 3 Carageenan 0.10.1 0.1 0.1 0.2 Pigment 0.1 0.1 0.1 0.1 0.1 Polysorbate 80 0.4 0.5 0.30.3 0.3 Peppermint oil 0.8 2.7 0.6 3 3 Pullulan 78.3 74.1 87.4 63.5 71.9Microcrystalline 1.4 1.4 0.7 0.5 3 cellulose Lemon flavor 2 2 1.5 1.51.5 Galantamine HBr 10 Doxazosin 10 mesylate Tolterodine 2 tartrateParoxetine 20 hydrochloride Bambuterol 10 hydrochloride Total weight100.0 100.0 100.0 100.0 100.0

Example 28 to 32

As active pharmaceutical ingredients, pholcodine, butylscopolamine,fentanyl citrate, oxycodone HCl and buprenorphine HCl were added toprepare films having constitutional compositions shown in the followingTable 14. The sensory test was randomly conducted and test results werethat unpleasant aftertaste was well masked.

TABLE 14 Exam- Exam- Exam- Exam- Exam- ple 28 ple 29 ple 30 ple 31 ple32 Ingredient (wt. %) (wt. %) (wt. %) (wt. %) (wt. %) Sucralose 1.7 1.52 1.5 Aspartame 1.5 Acesulfame 0.5 0.6 0.7 0.5 potassium Rebaten 97% 2 22 2 1.5 Citric acid 0.2 0.2 0.2 0.6 0.6 Hydroxypropyl 2 2 3.8 3 7 starchSpan20 0.1 0.5 0.1 0.4 0.4 Menthol 0.4 2.3 0.3 3 3 Carageenan 0.1 0.10.1 0.1 0.2 Pigment 0.1 0.1 0.1 0.1 0.1 Polysorbate 80 0.4 0.5 0.3 0.30.3 Peppermint oil 0.8 2.7 1.6 3 3 Pullulan 78.3 74.1 86.4 71.5 74.9Microcrystalline 1 1 0.4 0.5 3.5 cellulose Beta 0.4 0.4 0.3 0.5 3.5cyclodextrin Lemon flavor 2 2 1.5 1 1.5 Pholcodine 10 Butylscopolamine10 Fentanyl citrate 0.2 Buprenorphine 12 HCl Oxycodone HCl 5 Totalweight 100.0 100.0 100.0 100.0 100.0

Example 33 to 37

As active pharmaceutical ingredients, hydromorphone HCl, escitalopramoxalate, rivastigmine tartrate, esomeprazole magnesium, and aripiprazolewere added to prepare films having constitutional compositions shown inthe following Table 15. The sensory test was randomly conducted and testresults were that unpleasant aftertaste was well masked.

TABLE 15 Exam- Exam- Exam- Exam- Exam- ple 33 ple 34 ple 35 ple 36 ple37 Ingredient (wt. %) (wt. %) (wt. %) (wt. %) (wt. %) Sucralose 1.7 1.62 1.5 Aspartame 1.5 Acesulfame 0.5 0.5 0.7 0.5 potassium Rebaten 97% 2 22 2 1.5 Citric acid 0.2 0.2 0.2 0.6 0.6 Hydroxypropyl 4 2 3.8 3 4 starchSpan20 0.1 0.5 0.1 0.4 0.4 Menthol 0.4 2.3 0.3 3 3 Carageenan 0.1 0.10.1 0.1 0.2 Pigment 0.1 0.1 0.1 0.1 0.1 Polysorbate 80 0.4 0.5 0.3 0.30.3 Peppermint oil 0.8 2.7 0.6 3 3 Pullulan 79.3 74.1 81.6 71.5 61.9Microcrystalline 4.4 1.4 3.7 2.5 2 cellulose Lemon flavor 2 2 1.5 1.51.5 hydromorphone Hcl 4 Escitalopram 10 oxalate Rivastigmine 3 tartrateAripiprazole 10 Esomeprazole 20 magnesium Total weight 100.0 100.0 100.0100.0 100.0

Example 38 to 42

As active pharmaceutical ingredients, zolmitriptan, rizatriptanbenzoate, telmisartan, risperidone and vardenafil HCl were added toprepare films having constitutional compositions shown in the followingTable 16. The sensory test was randomly conducted and test results werethat unpleasant aftertaste was well masked.

TABLE 16 Exam- Exam- Exam- Exam- Exam- ple 38 ple 39 ple 40 ple 41 ple42 Ingredient (wt. %) (wt. %) (wt. %) (wt. %) (wt. %) Sucralose 1.7 1.61 1.5 Neotame 1 1.5 Acesulfame 0.5 0.5 0.7 0.5 potassium Rebaten 97% 2 22 2 1.5 Citric acid 0.2 0.2 0.2 0.6 0.6 Hydroxypropyl 3 2 2.8 3 4 starchSpan20 0.1 0.5 0.1 0.4 0.4 Menthol 0.4 2.3 0.3 3 3 Carageenan 0.1 0.10.1 0.1 0.2 Pigment 0.1 0.1 0.1 0.1 0.1 Polysorbate 80 0.4 0.5 0.3 0.30.3 Peppermint oil 0.8 2.7 0.6 3 3 Pullulan 79.3 74.1 68.6 79.5 79.4Microcrystalline 6.9 1.4 0.7 3.5 2 cellulose Lemon flavor 2 2 1.5 1.51.5 Zolmitriptan 2.5 Rizatriptan 10 benzoate Telmisartan 20 Risperidone1 Vardenafil HCl 2.5 Total weight 100.0 100.0 100.0 100.0 100.0

Example 43 to 48

As active pharmaceutical ingredients, benzocain, loratidine,phenylephrine HCl, diphenhydramine HCl, Dextromethorphan hydrobromide,and cetrizine HCl were added to prepare films having constitutionalcompositions shown in the following Table 17. The sensory test wasrandomly conducted and test results were that unpleasant aftertaste waswell masked.

TABLE 17 Exam- Exam- Exam- Exam- Exam- Exam- ple 43 ple 44 ple 45 ple 46ple 47 ple 48 Ingredient (wt. %) (wt. %) (wt. %) (wt. %) (wt. %) (wt. %)Sucralose 1.7 1.6 1 1.5 1 1 Neotame 0.5 0.5 Acesulfame 0.5 0.5 0.7 0.5potassium Rebaten 97% 2 2 2 2 1.5 1.5 Citric acid 0.2 0.2 0.2 0.6 0.60.6 Hydroxypropyl 5 2 5 3 4 4 starch Span20 0.1 0.5 0.1 0.4 0.4 0.4Menthol 0.4 1.3 0.3 3 3 3 Carageenan 0.1 0.1 0.1 0.1 0.2 0.2 Pigment 0.10.1 0.1 0.1 0.1 Polysorbate 80 0.4 0.5 0.3 0.3 0.3 0.3 Peppermint oil0.8 2.7 0.6 3 3 3 Pullulan 79.3 75.1 78.6 79.5 79.4 72 Micro- 4.4 1.44.5 2 2 2 crystalline cellulose Lemon flavor 2 2 1.5 1.5 1.5 1.5Benzocain 3 Loratadine 10 Phenylephrine 5 HCl Diphen- 2.5 hydramine HClDextro- 2.5 methorphan hydrobromide Cetrizine HCl 10 Total weight 100.0100.0 100.0 100.0 100.0 100.0

In terms of dose acceptability, the inventive oral film dosage exhibitedmore excellent effects of masking a nasty taste. As is apparent from theforegoing description, the quickly soluble oral film dosage according tothe present invention has advantages of efficiently masking a nastytaste, and being easily produced by simple processes at low cost.Therefore, the inventive oral film dosage may be effectively used invarious applications such as an oral cleanser, a bad breath remover, acarrier for nutrient supplementary agent, and a tongue solubleformulation enabling absorption of drugs in the oral cavity as well asthe stomach and bowels, and so forth.

While the present invention has been described with reference toexemplary embodiments, it will be understood by those skilled in the artthat various modifications and variations may be made therein withoutdeparting from the scope of the present invention as defined by theappended claims.

1. A quickly soluble oral film dosage, comprising: at least onewater-soluble polymer; at least one active pharmaceutical ingredient; astevioside based sweetener as an aftertaste enhancer; and at least oneprimary sweetening agent as a taste masking agent.
 2. The oral filmdosage according to claim 1, wherein the stevioside based sweetenerincludes at least one selected from a group consisting of stevioside,enzyme degradable stevioside, rebaudioside A and products containingthem with high contents.
 3. The oral film dosage according to claim 1,wherein the primary sweetening agent is at least one selected from agroup consisting of aspartame, acesulfame salts, neotame, sucralose,thaumatine, saccharine, licorice extract, neohesperidin and moneyline.4. The oral film dosage according to claim 1, wherein the film contains0.1 to 10 wt. % of the stevioside based sweetener and the primarysweetening agent, respectively, relative to the total weight of thequickly soluble film and wherein the stevioside based sweetener and theprimary sweetening agent are contained in a relative ratio by weight(w/w) of 1:3 to 3:1.
 5. The oral film dosage according to claim 1,wherein the water-soluble polymer is at least one selected from a groupconsisting of pullulan, gelatin, pectin, low viscosity pectin,hydroxypropylmethyl cellulose, low viscosity hydroxylpropylmethylcellulose, hydroxyethyl cellulose, hydroxypropyl cellulose,carboxymethyl cellulose, polyvinylalcohol, polyacrylic acid, methylmethacrylate copolymer, carboxyvinyl polymer, polyethyleneglycol,alginic acid, low viscosity alginic acid, sodium alginate, modifiedstarch, casein, whey protein extract, soy protein extract, zein, levan,elsinan, gluten, acacia gum, carageenan, Arabic gum, guar gum, locustbean gum, xanthan gum, gellan gum and agar.
 6. The oral film dosageaccording to claim 5, wherein the water soluble polymer is at least oneselected from a group consisting of pullulan, gelatin, low viscositypectin, low viscosity alginic acid and low viscosityhydroxylpropylmethyl cellulose.
 7. The oral film dosage according toclaim 1, wherein the active pharmaceutical ingredient is at least oneselected from a group consisting of diabetic remedy; insomnia remedy;genito-urinary remedy; obesity remedy; enzyme; gastric ulcer remedy;cough remedy and expectorant; dermal disorder remedy; antinausea drug;antidepression drug; antihistamine drug; antipyretic, analgesic andantiphlogistic remedy; hormone drug; circulatory organ remedy;gastrointestinal remedy; psychoneurotic drug; impotency remedy;osteoporosis remedy; arthritis remedy; epilepsy remedy; muscle relaxingagent; cerebral function enhancer; schizophrenia remedy;immuno-suppression agent; antibiotic agent; anticancer agent;Supportives in tumor therapy; vaccine; oral cleanser; anemia remedy;constipation remedy; vitamin; nutrient; probiotic preparation;multi-symptom cold/flue medications; and health functional foods.
 8. Theoral film dosage according to claim 7, wherein the active pharmaceuticalingredient is at least one selected from a group consisting oftriclosan, cetylpyridium chloride, domiphen bromide, quaternary ammoniumsalt, zinc compounds, sanguinarine, fluoride, alexidine, octenidine,EDTA, aspirin, acetaminophen, ibuprofen, ketoprofen, diflunisal,fenoprofen calcium, naproxen, tolmetin sodium, indomethacin,benzonatate, caramiphen, edisylate, menthol, dextromethorphanhydrobromide, chlophedianol hydrochloride, diphenhydramine,pseudoephedrine hydrochloride, phenylephrine, phenylpropanolamine,pseudoephedrine sulfate, bromophenylamine maleate, chlorophenylaminemaleate, carbinoxamine maleate, clemastine fumarate, dexchlorpheniraminemaleate, diphenhydramine hydrochloride, diphenhydramine citrate,diphenylpyraline hydrochloride, doxylamine succinate, promethazinehydrochloride, pyrilamine maleate, tripelennamine citrate, triprolidinehydrochloride, acrivastine, loratadine, brompheniramine,dexbrompheniramine, guaifenesin, ipecac, calcium iodide, terpinehydrate, loperamide, famotidine, ranitidine, omeprazole, lansoprazole,aliphatic alcohol, nicotine, caffeine, strychnine, picrotoxin,pentylenetetrazol, phenylhydantoin, phenobarbital, primidone,carbamazepine, ethosuximide, methosuximide, phensuximide, trimethadione,diazepam, benzodiazepine, phenacemide, pheneturide, acetazolamide andsulthiame, bromide levodopa, amantadine, morphine, heroin,hydromorphone, methophone, oxymorphone, levorphanol, codeine,hydrocodone, xycodone, nalorphine, naloxone, naltrexone, salicylate,phenylbutazone, indomethacin, phenacetin, chloropromazine,methotrimeprazine, haloperidol, clozapine, reserpine, imipramine,tranylcypromine, phenelzine, lithium, apomorphine, sildenafil,tadalafil, vardenafil, ondansetron, donepezil, zolpidem tartrate,granisetron, montelukast, pholcodine, butylscopolamine, fentanylcitrate, oxycodone hydrochloride, buprenorphine hydrochloride,escitalopram oxalate, rivastigmine tartrate, esomeprazole magnesium,aripiprazole, zolmitriptan, rizatriptan benzoate, telmisartan,risperidone, benzocaine, cetirizine hydrochloride, bambuterolhydrochloride, galantamine hydrobromide, lercanidipine hydrochloride,paroxetine hydrochloride, meloxicam, tolterodine tartrate, doxazosinmesylate, and pharmaceutically available salts thereof.
 9. The oral filmdosage according to claim 8, wherein one of the ondansetron salts is anondansetron hydrochloride, and a quickly soluble film including theondansetron hydrochloride as the active pharmaceutical ingredient hasbioequivalence.
 10. The oral film dosage according to claim 8, whereinone of the montelukast salts is a montelukast sodium, and a quicklysoluble film including the montelukast sodium as the activepharmaceutical ingredient has bioequivalence.
 11. The oral film dosageaccording to claim 8, wherein one of the sildenafil salts is asildenafil citrate, and a quickly soluble film including the sildenafilcitrate as the active pharmaceutical ingredient has bioequivalence. 12.The oral film dosage according to claim 1, wherein the quickly solublefilm further comprises at least one of additives.
 13. The oral filmdosage according to claim 12, wherein the additives comprise at leastone selected from a group consisting of a filler, a plasticizer, asecondary sweetening agent, an acidic agent, a flavor, an emulsifier, apigment and a cooling agent.
 14. The oral film dosage according to claim13, wherein the filler is at least one selected from a group consistingof microcrystalline cellulose, cellulose polymer, magnesium carbonate,calcium carbonate, limestone powder, silicate, clay, talc, titaniumdioxide and calcium phosphate.
 15. The oral film dosage according toclaim 13, wherein the plasticizer is at least one selected from a groupconsisting of sorbitol, maltitol, xylitol, glycerin, polyethyleneglycol,propyleneglycol, hydrogenated starch syrup, starch syrup, triacetin,glycerol oleate, sucrose fatty acid ester and double chain fatty acid.16. The oral film dosage according to claim 13, wherein the secondarysweetening agent is at least one selected from a group consisting ofsugar, glucose, maltose, oligosaccharides dextrin, alpha cyclodextrin,beta cyclodextrin, gamma cyclodextrin, hydroxypropy beta cyclodextrin,methyle beta cyclodextrin, cluster dextrin, indigestible dextrin,hydrogenated indigestible dextrin, invert sugar, fructose, lactose,galactose, starch syrup, sorbitol, maltitol, xylitol, erythritol,hydrogenated starch syrup, mannitol and trehalose.
 17. The oral filmdosage according to claim 13, wherein the acidic agent is at least oneselected from a group consisting of citric acid, malic acid, fumaricacid, tartaric acid, ascorbic acid, succinic acid, adipic acid andlactic acid.
 18. The oral film dosage according to claim 13, wherein theflavor is a natural flavor, an artificial flavor or a mixture thereof.19. The oral film dosage according to claim 13, wherein the emulsifieris at least one selected from a group consisting of glycerin fatty acidester, sucrose fatty acid ester, lecithin, enzyme treated lecithin,polysorbate, sorbitan fatty acid ester and propyleneglycol